Publications
Much has been published about biosimilars since their introduction in the early 2000s.
To read more about the background, development processes and regulations around biosimilars, please see
Biosimilars Development and Evidence
Category: Biosimilars Development and evidence
European Commission
Biosimilars in the EU: Information Guide for Healthcare Professionals
Consensus Information Paper 2019. European Medicines Agency (EMA). Biosimilars in the EU: Information guide for healthcare professionals
Since the EU approved the first biosimilar medicine (‘biosimilar’) in 2006, the EU has pioneered the regulation of biosimilars. Over the past 10 years, the EU has approved the highest number of biosimilars worldwide, amassing considerable experience of their use and safety.
This guide has been jointly developed by the EMA and European commission with the objective of providing healthcare professionals with reference information on both the science and regulation underpinning the use of biosimilars.
Category: Biosimilars Development and evidence
Kurki P, van Aerts L, et al.
Interchangeability of Biosimilars: A European Perspective
BioDrugs 2017;31:83-91
The introduction of biosimilars has shown that even complex proteins used for chronic disease treatment can be successfully copied. This in turn triggered discussions on aspects such as interchangeability between biosimilars and their reference products as well as immunogenicity profile of biosimilars.
Category: Biosimilars Development and evidence
Vulto AG and Jaquez A
The Process Defines the Product: What Really Matters in Biosimilar Design and Production?
Rheumatology (Oxford) 2017 1;56
Critical quality attributes (CQA) of a biologic are subject to post-translational variations at the cellular and/or manufacturing level. One of the founding principles of the biosimilarity exercise is to closely match the biosimilar’s fingerprint with that of its reference product. Therefore, and in contrast to original biological agents, the emphasis in biosimilar development is on analytical and nonclinical attributes. The manufacturer's ability to provide consistent production and quality control will greatly influence the acceptance of its biosimilar products.
Category: Biosimilars Development and evidence
Wolff-Holz E, Tiitso K, et al
Evolution of the EU Biosimilar Framework: Past and Future.
BioDrugs 2019;33:621-634
The authors of this review focused on the nature and extent of clinical confirmation, in addition to analytical and functional data required by the European Medical Agency (EMA) for the approval of biosimilar products.
Category: Biosimilars Development and evidence
European Commission
What You Need to Know about Biosimilar Medicinal Products
Consensus Information Paper 2019. What you need to know about biosimilar Medicinal Products
The European Commission has prepared this paper in order to provide payers, physicians and patients with adequate information on biosimilars. It gives a detailed overview of biologics and biosimilars, regulation and development of biosimilars, potential economic consequences of using biosimilars as well as Q&A sections for each of the key stakeholders.
Category: Biosimilars Development and evidence
Weise M, Kurki P, et al.
Biosimilars: The Science of Extrapolation
Blood 2014;124:3191–6
This article addresses the concerns frequently raised in the medical community regarding the use of biosimilars in extrapolated indications and explains the underlying scientific and regulatory decision making, including some real-life examples from recently licensed biosimilars. This article is an extension to a paper published previously by Weise et al. (Blood 2012;120:5111–5117) which explained the principles of biosimilar development in general.
Category: Biosimilars Development and evidence
O'Callaghan J, Barry SP, et al.
Regulation of Biosimilar Medicines and Current Perspectives on Interchangeability and Policy.
Eur J Clin Pharmacol 2019;75:1-11
The differences between FDA and EMA interchangeability recommendations for biosimilar therapeutics are discussed in this review. USA federal policy is contrasted with that of the EMA – ‘interchangeable products’ are evaluated in the former, whereas the EMA does not assess interchangeability. Policies promoting the use of biosimilar medicines in a number of European countries, the USA and Australia are discussed.
Category: Biosimilars Development and evidence
Schiestl M, Stangler T, et al.
Acceptable Changes in Quality Attributes of Glycosylated Biopharmaceuticals
Nat Biotechnol 2011;29:310–2
This study analyses the quality profiles of the glycosylated biologics darbepoetin alfa, rituximab and etanercept and debates acceptable variations in quality attributes. This data, sourced from the market between 2007 and 2010, provides examples of acceptable variations for products that have remained on the market with unchanged product labels.
Category: Biosimilars Development and evidence
Barbier L, Ebbers HC, et al.
The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review.
Pharmacol Ther 2020;108(4):734-755.
To date, no consensus exists among stakeholders about switching patients between reference biological products (RPs) and biosimilars, which may have been curbing the implementation of biosimilars in clinical practice. This study is the first available synthesis on the available data on switching and assesses whether switching patients from a RP to its biosimilar or vice versa affects efficacy, safety, or immunogenicity outcomes.
Category: Biosimilars Development and evidence
Vezér B, Buzás Z, et al.
Authorized Manufacturing Changes of Therapeutic Monoclonal Antibodies (mAbs) in European Public Assessment Report (EPAR) Documents
Curr Med Res Opin 2016;32:829–34
This study investigated number and types of manufacturing changes for originator monoclonal antibodies based on European Public Assessment Report documentation and ascertained the level of risk these changes might impart. The study highlighted EMA's significant experience of process changes for originator monoclonal antibodies and the impact they may have on the efficacy and safety of biologicals. This experience is valuable for biosimilar product development.
Nocebo Effect
Category: Nocebo Effect
Sharma A, Kumar N, et al.
Need of Education on Biosimilars Amongst Ophthalmologists: Combating the Nocebo Effect.
Eye (Lond). 2020;34:1006-1007
In this comment, authors describe the transformative effect of biologics in the treatment of diseases of the retina and the efforts to address patients’ non-compliance, driven by high-cost of biologics, through developing new biologics as well as biosimilars of already existing originators. Education around biosimilars among ophthalmologists need to be revisited and topics such as nocebo addressed.
Category: Nocebo Effect
Benedetti F, Piedimonte A, et al.
The Neurobiological Underpinnings of Placebo and Nocebo Effects.
Semin Arthritis Rheum. 2019 Dec;49(3S):S18-S21
In this study, authors discuss the effects of language and psychosocial context on patients’ response to their treatment and course of disease.
Category: Nocebo Effect
Spanou I, Mavridis T, et al.
Nocebo in Biosimilars and Generics in Neurology: A Systematic Review.
Front Pharmacol. 2019 Jul 24;10:809.
A systematic review where the aim was to estimate the magnitude of nocebo in generics and biosimilars available to treat different neurological diseases and propose strategies to minimize its prevalence both in clinical practice and clinical trials.
Category: Nocebo Effect
Pouillon L, Danese S, et al.
Consensus Report: Clinical Recommendations for the Prevention and Management of the Nocebo Effect in Biosimilar-treated IBD Patients
Aliment Pharmacol Ther 2019;49:1181-1187
The nocebo effect is under-recognised in the era of biosimilars, although it may negatively impact on the cost-savings of biosimilars. Future research should focus on the magnitude, the risk factors, the impact, and the management of the nocebo effect in biosimilars-treated IBD patients.
Category: Nocebo Effect
Rezk MF and Pieper B.
To See or NOsee: The Debate on the Nocebo Effect and Optimizing the Use of Biosimilars.
Adv Ther 2018;35:749–753
The authors take a closer look at the negative impact of the nocebo effect, as reported in a number of clinical trials, and its implications on patients’ perception when switching from an originator biologic to a biosimilar.
Category: Nocebo Effect
Rezk MF and Pieper B.
Treatment Outcomes with Biosimilars: Be Aware of the Nocebo Effect.
Rheumatol Ther 2017;4:209–218
The authors focus on the wide adoption of biosimilars, the re-emergence of the nocebo effect and the implications it may have on both patients and physicians’ perceptions as well as on treatment success. The authors also provide practical strategies and recommendations to raise awareness and to limit the nocebo effect.
Category: Nocebo Effect
Kristensen LE, Alten R, et al.
Non-pharmacological Effects in Switching Medication: The Nocebo Effect in Switching from Originator to Biosimilar Agent.
BioDrugs 2018;32:397–404
This review investigates the nocebo effect, defining the term and considering it in the process of switching from originator products to biosimilars. Three strategies aimed at mitigating the nocebo effect are discussed: positive framing, increasing patients and HCPs understanding of biosimilars and managed switching programs.
Category: Nocebo Effect
Odinet JS, Day CE, et al.
The Biosimilar Nocebo Effect? A Systemic Review of Double-blinded versus Open-label Studies.
J Manag Care Spec Pharm 2018;24:952–9
This publication reviews 31 trials, involving a total of 3,271 patients, to analyse the potential role of a nocebo effect in the arising of treatment-emergent adverse events in switching studies.